Organic compound of antimony and process for making it



Patented Oct. 5, 1943 l nhfi or eF nb o k y N- 6-, s en to.Parke,,Davis 8:v Company, Detroit, M ich a corporation [of Michigan NeDrawing. Application March 3l;

ScriaLNo. 386,063;

8 Claims.

This invention, whichiorms acontinuation in part of my applicationfiledsMay 27, 1940, Serialv No. 337,445, relates generally .to.a,series.of neworganic compounds of antimony: and to processes. for their manufacture, these compoundsiembodya ing certain properties which render-themuseful asmedicinal and insecticidal agents.

One of the primary objects of thisinvention is to provide a method, and thereaction products thereof, wherein compounds of antimony are combined with an alcoholamine, or a C011. densation product thereof, to formnew com-. pounds capableof entering into stable aqueous, solution. This property would be desirable. in, medicinal compounds to be administered paren terally.

A contrasting, but not contradictory, object of this invention is to provide a method, and the reaction products thereof, wherein compounds of antimony are combined withan alcoholamine,

or a condensation product thereof, to form'new:

compounds of antimony, in liquid form, which are insoluble in water. Such compounds would. be of definite use inthe permanent impregna tion of porous materialswhich-are so employed thatthey are in more or lessconstant contact with water.

A more specific object of the-instant invention is toprovide a composition of matter consisting of the reactionproduct ofan antimony compound and triisoprop'anolamine in an inert solvent, such as propylene glycol, as a reactionmedium. 7

- A further object of the-inventionis to provide a process whereby inorganic salts of antimony may, through chemicalcombination, be converted toorganic compounds, which latter compounds possess none of theirritant or caustic properties that may. have been inherent in the inorganic salt.

A still further object of the. invention is to hemical mbmation; hat n w, compounds: ar o dawhichl tt r. comp und o sess 2. .1.

l gical andvtherapeutic. n opertiesmor de i able. I

than th seof th orisin lc mpoundsa Yet not er: b ect; of the invention sqto me.- pare, through: chemical; combination, certaincompounds of antimony whichv may. be r processed into forms suitable for medicinal purposes; either through conversion. into, sterile injectiblc, solution, .orinto forms. s te r raladm n s rat on Suchc mp nds; naturally u e them elv s. f ru e inthose patholo cal. ndi ions; wherein v pr per ie .ofv ntimonyare of known, or-suspccted therapeutic value; such; conditions being readily apparent; to. those skilled; in human or animal medicine,

This inventionhas; for a further aim torprovide a: series 015- substantially homologoustoiomr pounds wherein: antimony may beincorporated in. either the trivalent ;or pentavalent; state. This achievement is of considerable. importance; from a therapeutic standpoint since itiis. welt estab: lished that various; disease conditions; respond difierently .to the trivalent and; pentavalent forms, of antimony. s By: way of definition, the, term ,alcoholamine="r as used herein, refers to that class. of aminestin which one or more of. theorganic radicals cone;

tains.anhydroxylgroupi. The method. contemplated. by this invention involves. the reaction'of an. antimony compound with triisopropanolan ine in the. presence of propylene glycol. Thefunctionof the latter is merely that ota reaction medium and; solvent for the final reaction product. This is; demon: stratedby the fact; that the reaction. may! be carried outdn. the; total absence. of; solvent, or in the: presence of water, ethylene glycol-:01; die ethylene. glycol as; the solvent. Therefore, propylenelycol is1unesszgntialxtothe process, is employed simply, as a convenience, and. may be dispensed with or replaced; by. other suitablesoh vents. v

. Triisopropanolamine is. employedinthetype process since I: have. found it; most suitableior the production. ofstable products. .-.However, other alcpholamineswe. gmonoethanolamine, diethanolamine, triethanolamine, phenyl ethe anolamine, phenyl diethanolamine, ethyl henyl ethanolamineeeor a condensation product of such'compoundsee-e. g. morpholinefiarel capable of reacting withantimony compounds and..may besubstitutedfor thetriisopropanolamine; As a. matter of fact, for sometcommercial purposes, triethanolamine, r one. of 1 the. other cheaper. a1

coholamines, may be preferred to triisopropanolamine.

In the practice of the invention, it is generally necessary or advisable to apply heat to the mixture of chemicals to efiect or hasten reaction. However, certain of the more reactive compounds of antimony-e. g. antimony pentachloridereact spontaneously in an exothermic manner with triisopropanolamine, and in these cases the external application of heat is unnecessary. I

In the course of the research conducted, a large number of antimony compounds have been combined with triisopropanolamihe by means of the type process described below. Such representative compounds as antimony trichloride, antimony oxychloride, antimony pentachloride, antimonial catechol, antimonial catechol chloride and antimony tribromide have been successfully employed. On the other hand, certain compounds, such as the sulfide of antimony, do not directly enter into the-reaction under the conditions employed. As a result of this discovery I have reached the conclusion that compounds of antimony are generally capable of reacting with triisopropanolamine, but the degree of reaction is subject to the influence of the elements or radicals afiixed to the antimony in the compounds used.

By way of example rather than by way of limitation, -I will detail the process for combining antimonial catechol with triisopropanolamine:

Antimonial catechol, prepared in the usual manner, is thoroughly washed with cold, distilled water, then with alcohol and ether, and dried in vacuum. A mixture of 16 gms. of triisopropanolamine and 20 cc. of propylene glycol are warmed on a water bath, or other suitable source of heat, until solution is effected. To avoid possible decomposition of the reaction product, it is advisable to keep the temperature below 100 C. throughout the process. To this mixture is added 6.5 gms. of antimonial catechol and the whole is stirred'until the antimonial catechol is dissolved. The resultant product is filtered through filter paper, using a Buchner funnel and suction. The filtrate, which represents the. reaction productdissolvedin. a mixture of propylene glycol and excess -urireacted triisopropanolamine, is stored in an amber glass bottle.

Other compounds of antimony are readily substituted in the process by employing such quan tities of these other compounds as willcontain amounts of antimony equivalent to that contained in antimonial catechol. However, I wish to emphasize that the quantities I have employed in the above process are not critical, but are arbitrarily chosen for convenience. As a matter of fact, in commercial application of the invention, it will probably be deemed advisable to raise the ratio of antimony to triisopropanolamine, since'the triisopropanolamine is often the most expensive of the materials used.

Throughout this invention I have claimed a chemical ,reactionbetween the antimony compounds and the triisopropanolamine; That actual chemical reaction, rather than simple solution, is involved is borne out by several observations. I have already mentioned that in several cases considerable heat is evolved, which, though not conclusive evidence, tends to point to a chemical reaction taking place. Further evidence of chemical reaction is the alteration of certain properties of the original antimony compounds employed. Thus, those compounds which are originally water insoluble-e. g. antimonial catepropanolamine, needle-like white crystals separate on standing. These crystals have been identified as the hydrochloride of the excess, unreacted triisopropanolamine, indicating the formation of hydrogen chloride in the course of ated hydrogen chloride.

the reaction between the chlorides of antimony and triisopropanolamine. This formation of hydrogen chloride points definitely to a double decomposition reaction with the elimination of a chloride ion from the antimony chloride and the elimination of a hydrogen ion from the triisopropanolamine.

The resultant reaction products are complex in nature and their ultimate chemical composition has not been determined, but I have observed and noted certain of their characteristics. Though the properties of the reaction products are, naturally, somewhat .dependent upon the original antimony compound and alcoholamine employed in the reaction, the following general observations may be made:

When prepared in accordance with the type process presented above, the resultant product is a somewhat viscous liquid which retains the characteristic odor of the triisopropanolamine, the latter being present in excess, except where this odor is obscured by the acrid odor of liber- The color of the compounds produced ranges from a light straw shade to the deeper amber shades.

' The solubility of these compounds in water depends upon the solubility of the alcoholamine employed. Generally, those antimony compounds prepared from alcoholaminescontaining only alkyl radicals are readily soluble in absolute alcohol, acetone, glycerine and chloroform, but only slightly soluble in ether and toluene. Their aqueous solutions are not decomposed by boiling and are compatible with blood plasma. Again by way of example rather than by way of limitation, I have demonstrated that doses of 1 c. c. to 5 c. c. of an aqueous solution of triisopropanolamine-antimonial"catechol, containing 8.5 mgms. of antimony per 0. 0., may be injected intravenously into dogs over a period of time without producing any ill effects. Further, I have demonstrated that if employed on dogs infested with Dirofilaria immitis this solution will free the blood stream of the infested animal of the larvae of Dirofilaria immitis.

On the other hand, reaction products of antimony compounds and alcoholamines containing one or more aromatic groups are generally insoluble in water. Far from being an undesirable property, this insolubility in water may be most desirable for certain specific purposes-e. g. impregnation of porous materials which of necessity are subject to more or less constant contact with water.

Having thus described the invention, I claim:

1. A method of producing a composition of matter of the character described, which consists in adding antimonial catechol to triisopropanolamine and heating the mixture until the reaction is completed.

2. A method of producing a composition of matter of thecharacter described, which consists in adding antimonial catechol to a mixture of triisopropanolamine and propylene glycol, and heating the whole until the reaction is completed.

3. A composition of matter consisting of the reaction product of antimonial catechol and triisopropanolamine. v

4. A composition of matter consisting of the reaction product of antimonial catechol and triisopropanolamine in propylene glycol.

5. A method of producing a composition of JOSEPH GEORGE FEINBERG. 

